Pivotal Study of N-acetyl-L-leucine for CACNA1A

NCT07221292 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: IB1001-3042025-523828-51
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 5

Brief Summary

A pivotal, randomized, double-blind, placebo-controlled, multi-center therapeutic study for patients age 4 and older with a confirmed diagnosis of CACNA1A. The objective of this study is to evaluate the safety, tolerability and efficacy of N-acetyl-L-leucine (IB1001) compared to standard of care.

Conditions

CACNA1A; Spinocerebellar Ataxia Type 6; Episodic Ataxia Type 2; Familial Hemiplegic Migraine-1

Keywords

CACNA1A; Episodic Ataxia Type 2; Spinocerebellar Ataxia Type 6

Outcome Measures

Primary Outcomes (1)

• Scale for the Assessment and Rating of Ataxia

  The Scale for Assessment and Rating of Ataxia has 8 items that are related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements, and heel-shin test. The range is 0-40 points, with a lower score representing neurological improvement and a higher score representing neurological worsening.

  End of Period I (week 12) vs. End of Period 2 (week 24)

Secondary Outcomes (4)

• Spinocerebellar Ataxia Functional Index (SCAFI)

  End of Period I (week 12) vs. End of Period 2 (week 24)

• Physician's / Caregiver's / Patient's Clinical Global Impressions (CGI)

  End of Period I (week 12) vs. End of Period 2 (week 24)

• EuroQuol- 5 Dimension (EQ-5D) Quality of Life Scale

  End of Period I (week 12) vs. End of Period 2 (week 24)

• Neuro Quality of Life - Upper Extremity Function (NeuroQOL-UEF)

  End of Period I (week 12) vs. End of Period 2 (week 24)

Other Outcomes (4)

• Scale for Ocular Motor Disorders in Ataxia

  End of Period I (week 12) vs. End of Period 2 (week 24)

• Epworth Sleepiness Scale

  End of Period I (week 12) vs. End of Period 2 (week 24)

• Frequency of Seizures

  End of Period I (week 12) vs. End of Period 2 (week 24)

Study Arms (2)

N-acetyl-L-leucine (IB1001)

EXPERIMENTAL

Oral administration (granule in a sachet for suspension in water, orange juice, or almond milk). Patients will receive a total daily dose of 2-4 g/day based on weight-tiered doses.

Drug: N-Acetyl-L-Leucine

Placebo

PLACEBO COMPARATOR

Oral administration (granule in a sachet for suspension in water, orange juice, or almond milk). Patients will receive a total daily dose of 2-4 g/day based on weight-tiered doses.

Other: Placebo

Interventions

N-Acetyl-L-Leucine DRUG

N-Acetyl-L-Leucine is a modified amino-acid ester that is orally administered (granules for suspension in a sachet)

N-acetyl-L-leucine (IB1001)

Placebo OTHER

Matching Placebo Sachet

Placebo

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent signed by the patient and/or their legal representative / parent/ impartial witness.
• Male or female aged ≥4 years with a genetically-confirmed diagnosis of a CACNA1A Disorder (including patients with loss-of-function and fain-of-function mutations, e.g. Episodic Ataxia Type 2 (EA2), Familial Hemiplegic Migraine Type 1, Spinocerebellar Ataxia type C (SCA6), Developmental and Epileptic encephalopathy 42 (DEE42), Congenital ataxia or cerebellar hypoplasia due to a CACNA1A mutation) at the time of signing informed consent.
• Females of childbearing potential, defined as a premenopausal female capable of becoming pregnant, will be included if they are either sexually inactive (sexually abstinent for 14 days prior to the first dose and confirm to continue through 28 days after the last dose) or using one of the following highly effective contraceptives (i.e. results in \<1% failure rate when used consistently and correctly) 14 days prior to the first dose continuing through 28 days after the last dose:
• intrauterine device (IUD);
• surgical sterilization of the partner (vasectomy for 6 months minimum);
• combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal);
• progestogen only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable);
• intrauterine hormone releasing system (IUS);
• bilateral tubal occlusion.
• Females of non-childbearing potential who have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
• hysteroscopic sterilization;
• bilateral salpingectomy;
• hysterectomy;
• bilateral oophorectomy; OR be postmenopausal with amenorrhea for at least 1 year prior to the first dose and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status. FSH analysis for postmenopausal women will be done at screening. FSH levels should be in the postmenopausal range as determined by the central laboratory.
• If male, patient agrees not to donate sperm from the first dose until 90 days after their last dose.

You may not qualify if:

• Patients who have any known hypersensitivity or history of hypersensitivity to:
• Acetyl-Leucine (DL-, L-, D-) or derivatives.
• Excipients the IB1001 sachet (namely isomalt, hypromellose, and strawberry flavor).
• Excipients the placebo sachet (namely isomalt, hypromellose, strawberry flavor, citric acid, microcrystalline cellulose, lactose, denatonium benzoate).
• Simultaneous participation in another clinical study or participation in any clinical study involving administration of an investigational medicinal product (IMP; 'study drug') for at least 42 days prior to Visit 1. At the discretion of the Investigator, Medical Monitor, and Sponsor, the washout period for specific IMPs may be longer based on the pharmacological activity and pharmacokinetics of the drug.
• Patients with a physical or psychiatric condition which, at the Investigator's discretion and in consultation with the Medical Monitor and Sponsor (as applicable), may put the patient at risk, may confound the study results, or may interfere with the patient's participation in the clinical study, i.e. reliably perform study assessments.
• Known or persistent use, misuse, or dependency of medication, drugs, or alcohol.
• Current or planned pregnancy or women who are breastfeeding.
• Patients with severe vision or hearing impairment (that is not corrected by glasses or hearing aids) that, at the Investigator's discretion, interferes with their ability to perform study assessments.
• Patients who have been diagnosed with arthritis or other musculoskeletal disorders affecting joints, muscles, ligaments, and/or nerves that by themselves affect patient's mobility and, at the Investigator's discretion, interferes with their ability to perform study assessments.
• Patients at non-EU trial sites unwilling and/or not able to undergo a 42-day washout period from any of the following prohibited medication prior to Visit 1 (Baseline 1) and remain without prohibited medication through Visit 6.
• N-Acetyl-DL-Leucine (e.g. Tanganil®);
• N-Acetyl-L-Leucine (prohibited if not provided as IMP in the IB1001-304 trial);
• Patients at EU trial sites who have had any of the following prohibited medication 42-days prior to Visit 1 (Baseline 1) and unwilling and/or not able to remain without prohibited medication through Visit 6.
• N-Acetyl-DL-Leucine (e.g. Tanganil®);

Sponsors & Collaborators

• IntraBio Inc: lead

Study Sites (5)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

The University of Texas Health (UT Health)

Houston, Texas, 77030, United States

Location

University of Cologne

Cologne, 50937, Germany

Location

University of Giessen

Giessen, 35389, Germany

Location

University Hospital Bern Inselspital

Bern, 3010, Switzerland

Location

MeSH Terms

Conditions

Spinocerebellar Ataxias; Episodic Ataxia, Type 2

Interventions

acetylleucine

Condition Hierarchy (Ancestors)

Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Taylor Fields

CONTACT

+447426956369; tfields@intrabio.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled, double-blind, crossover, multi-center, study with 1:1 randomization of IB1001 plus SOC for 12-weeks versus placebo plus SOC for 12-weeks, followed by open-label extension study.

Study Record Dates

• First Submitted: October 24, 2025
• First Posted: October 27, 2025
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); CH (1); US (2)